Reports that estrogen may protect against age-associated declines in memory and against Alzheimer's Disease in postmenopausal women have led to increased interest in the effects of estrogen replacement therapy (ERT) on mental abilities and the brain. The use of ERT as a treatment for the emotional and physical symptoms associated with menopause provides a method for studying how estrogen may affect mental abilities. For example, recent findings from the Baltimore Longitudinal Study of Aging (BLSA) suggest that women using ERT show better memory as they age and are less likely to develop Alzheimer's Disease compared to similar women who do not use ERT. One limitation of such studies is that the women who participated in them elected on their own to receive ERT. Research suggests that such women tend to be better educated and to receive better health care than women who do not receive ERT. The bias is termed the "healthy user effect". To overcome this bias, we are conducting research studies looking at memory in women before and after ERT use. As the number of research studies confirming protective effects of ERT on memory increases, questions arise as to whether such effects vary with treatment duration and type of estrogen. All of the estrogen intervention studies to date have involved treatment durations of 2-6 months and oral estrogens, so there is no information on the effects of shorter-term ERT nor on the effects of different forms of ERT (e.g., trandermal patch). Some cognitive abilities vary with relatively abrupt fluctuations in estrogen over the 28-day menstrual cycle in young women. And though there is no reliable evidence in humans that memory abilities increase during phases of the menstrual cycle when estrogen is high, animal models of menopause indicate that ERT may have rapid effects on memory and brain areas subserving memory. Such studies suggest that positive effects of ERT may be observed after short-term treatment and that such treatment may affect brain regions that subserve memory. The primary aim of this study is to examine the relationship between estrogen and memory performance in healthy women aged 50-65. To this end, we propose to conduct a double-blind, placebo-controlled study in which we examine neuropsychological test performance of women before and after two weeks of treatment with an estrogen skin patch. To better understand how the brain changes with ERT use, we are using magnetic resonance imaging (MRI) to measure brain structure and positron emission tomography (PET) during memory task performance. Our aim is to better understand the effects of short-term ERT on memory and the brain.